title: Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy.
abstract: A subgroup of neutral lipid storage disease has been recently associated with myopathy (NLSDM) and attributed to mutations in the gene (PNPLA2) encoding an adipose triglyceride lipase involved in the degradation of intracellular triglycerides. Five NLSDM patients have been described thus far and we reported three additional patients. A 44-year old Iranian woman and two Italian brothers, aged 40 and 35, presented with exercise intolerance and proximal limb weakness, elevated CK levels, and Jordan's anomaly. Muscle biopsies showed marked neutral lipid accumulation in all patients. The 10 exons and the intron-exon junctions of the PNPLA2 gene were sequenced. Two novel homozygous mutations in exon 5 of PNPLA2 gene were found (c.695delT and c.542delAC). Both mutations resulted in frameshifts leading to premature stop codons (p.L255X and p.I212X, respectively). These mutations predict a truncated PNPLA2 protein lacking the C-terminal hydrophobic domain. These findings indicate that NLSDM is rare, but genetically heterogeneous.
authors.affiliation: Department of Clinical and Therapeutic Medicine, Università di Roma La Sapienza, 00161 Rome, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Campagna
authors.forename: Luisa
authors.initials: L
authors.lastname: Nanni
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quagliarini
authors.forename: Elena
authors.initials: E
authors.lastname: Pennisi
authors.forename: Constantine
authors.initials: C
authors.lastname: Michailidis
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Carlo
authors.initials: C
authors.lastname: Casali
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
mesh_terms: D000328:Adult; D001706:Biopsy; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D020140:Lysosomal Storage Diseases, Nervous System / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000217:Acyltransferases
chemical_list: D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases